Adaptive immune responses to hepatitis C virus: from viral immunobiology to a vaccine.
Hepatitis C virus (HCV) causes chronic infection in approximately two-thirds of cases, leading to chronic hepatitis, liver cirrhosis, liver disease, liver failure, and hepatocellular carcinoma in a substantial proportion of the 170 million HCV-infected individuals worldwide. It is generally accepted that the cellular immune response plays the most important role in determining the outcome of HCV infection. First, vigorous, multispecific and sustained CD4+ and CD8+ T-cell responses are associated with viral clearance. Second, depletion studies in chimpanzees, the only other host of HCV besides humans, have shown that both CD4+ and CD8+ T-cells are required for virus elimination. Third, the host's human leukocyte antigen alleles, which restrict the repertoire of CD4+ and CD8+ T-cell responses, influence the outcome of infection. Of note, protective immunity has been demonstrated in population-based studies, as well as in experimentally infected chimpanzees. Thus, a detailed understanding of the mechanisms contributing to the failure of the antiviral immune response should allow successful development of prophylactic and therapeutic vaccination strategies.
Thimme
Robert
R
Department of Medicine II, University Hospital Freiburg, D-79106 Freiburg, Germany.
Neumann-Haefelin
Christoph
C
Boettler
Tobias
T
Blum
Hubert E
HE
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D008099:Liver / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014761:Viral Hepatitis Vaccines / Q000276:immunology* / Q000627:therapeutic use*
D014761:Viral Hepatitis Vaccines